Characterization of phosphoglycan-containing secretory products ofLeishmania

Abstract

SUMMARYThis article presents an overview on phosphoglycan-containing components secreted by the insect and mammalian stages of several species ofLeishmania, the causative agents of leishmaniasis in the Old and New World. Firstly, promastigotes of all three species considered,L. mexicana, L. donovaniandL. major, shed lipophosphoglycan (LPG) into the culture medium possibly by release of micelles from the cell surface. Like the cell-associated LPG, culture supernatant LPG is arhphiphilic and composed of a lysoalkylphosphatidylinositol-phosphosaccharide core connected to species-specific phosphosaccharide repeats and oligosaccharide caps. Secondly, all three species release hydrophilic phosphoglycan. Thirdly, all three species appear to secrete proteins covalently modified by phosphosaccharide repeats and oligosaccharide caps. In the case of promastigotes ofL. mexicana, these components are organized as two filamentous polymers released from the flagellar pocket: the secreted acid phosphatase (sAP) composed of a 100 kDa phosphoglycoprotein and a protein- containing high-molecular-weight-phosphoglycan (proteo-HMWPG) and fibrous networks likewise composed of phosphoglycan possibly linked to protein. Structural analyses and gene cloning suggest that the parasites can covalently modify protein regions rich in serine and threonine residues by the attachment of phosphosaccharide repeats capped by oligosaccharides. We propose that the networks formedin vitrocorrespond to fibrous material previously demonstrated in the digestive tract of infected sandflies. In the case ofL. donovani, the sAP is also modified by phosphoglycans but contains neither proteo-HMWPG nor does it aggregate to filaments. Finally,L. mexicanaamastigotes release proteo-HMWPG via the flagellar pocket into the parasitophorous vacuole of infected macrophages. This material appears to be released into the tissue of the infected mammal upon rupture of infected macrophages during lesion development. This secretory product may contribute to the pathology of lesion development.